Ultrasound-guided therapeutic modulation of hepatocellular carcinoma using complementary microRNAs

Treatment options for patients with hepatocellular carcinoma (HCC) are limited, in particular in advanced and drug resistant HCC. MicroRNAs (miRNA) are non-coding small RNAs that are emerging as novel drugs for the treatment of cancer. The aim of this study was to assess treatment effects of two com...

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Bibliographic Details
Published in:Journal of controlled release 2016-09, Vol.238, p.272-280
Main Authors: Mullick Chowdhury, Sayan, Wang, Tzu-Yin, Bachawal, Sunitha, Devulapally, Rammohan, Choe, Jung Woo, Abou Elkacem, Lotfi, Yakub, Butrus Khuri, Wang, David S., Tian, Lu, Paulmurugan, Ramasamy, Willmann, Jürgen K.
Format: Article
Language:English
Subjects:
Animals
Antagomirs - administration & dosage
Antagomirs - therapeutic use
Antibiotics, Antineoplastic - therapeutic use
Cancer therapy
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - therapy
Complementary miRNA
Doxorubicin - therapeutic use
Drug Delivery Systems - methods
Drug resistance
Drug Resistance, Neoplasm
Gene Transfer Techniques
Genetic Therapy
Hep G2 Cells
Hepatocellular carcinoma
Humans
Lactic Acid - chemistry
Liver Neoplasms - genetics
Liver Neoplasms - therapy
Mice
Microbubbles
MicroRNAs - administration & dosage
MicroRNAs - genetics
MicroRNAs - therapeutic use
Polyglycolic Acid - chemistry
Ultrasonics - methods
Ultrasound
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Summary:Treatment options for patients with hepatocellular carcinoma (HCC) are limited, in particular in advanced and drug resistant HCC. MicroRNAs (miRNA) are non-coding small RNAs that are emerging as novel drugs for the treatment of cancer. The aim of this study was to assess treatment effects of two complementary miRNAs (sense miRNA-122, and antisense antimiR-21) encapsulated in biodegradable poly (lactic-co-glycolic acid) nanoparticles (PLGA-NP), administered by an ultrasound-guided and microbubble-enhanced delivery approach in doxorubicin-resistant and non-resistant human HCC xenografts. Proliferation and invasiveness of human HCC cells after miRNA-122/antimiR-21 and doxorubicin treatment were assessed in vitro. Confocal microscopy and qRT-PCR were used to visualize and quantitate successful intracellular miRNA-loaded PLGA-NP delivery. Up and down-regulation of miRNA downstream targets and multidrug resistance proteins and extent of apoptosis were assessed in vivo in treated human HCC xenografts in mice. Compared to single miRNA therapy, combination therapy with the two complementary miRNAs resulted in significantly (P
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2016.08.005